Renal cell carcinoma (RCC) is an aggressive genitourinary malignancy which has been associated with a poor prognosis, particularly in patients with metastasis, its major subtypes being clear cell RCC (ccRCC), papillary PCC (pRCC) and chromophobe RCC (chRCC). The presence of intracellular lipid droplets (LDs) is considered to be a hallmark of ccRCC. The importance of an altered lipid metabolism in ccRCC has been widely recognized. The elongation of very‑long‑chain fatty acid (ELOVL) catalyzes the elongation of fatty acids (FAs), modulating lipid composition, and is required for normal bodily functions. However, the involvement of elongases in RCC remains unclear. In the present study, the expression of ELOVL2 in ccRCC was examined; in particular, high levels of seven ELOVL isozymes were observed in primary tumors. Of note, elevated ELOVL2 expression levels were observed in ccRCC, as well as in pRCC and chRCC. Furthermore, a higher level of ELOVL2 was significantly associated with the increased incidence of a poor prognosis of patients with ccRCC and pRCC. The CRISPR/Cas9‑mediated knockdown of ELOVL2 resulted in the suppression of the elongation of long‑chain polyunsaturated FAs and increased LD production in renal cancer cells. Moreover, ELOVL2 ablation resulted in the suppression of cellular proliferation via the induction of apoptosis in vitro and the attenuation of tumor growth in vivo. On the whole, the present study provides new insight into the tumor proliferation mechanisms involving lipid metabolism, and suggests that ELOVL2 may be an attractive novel target for RCC therapy.
Oncology reports. 2021 Nov 29 [Epub]
Ken Tanaka, Shuya Kandori, Shotaro Sakka, Satoshi Nitta, Kozaburo Tanuma, Masanobu Shiga, Yoshiyuki Nagumo, Hiromitsu Negoro, Takahiro Kojima, Bryan J Mathis, Toru Shimazui, Makoto Watanabe, Taka-Aki Sato, Takafumi Miyamoto, Takashi Matsuzaka, Hitoshi Shimano, Hiroyuki Nishiyama
Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305‑8577, Japan., International Medical Center, University of Tsukuba Affiliated Hospital, Tsukuba, Ibaraki 305‑8576, Japan., Department of Urology, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki 309‑1793, Japan., Life Science Research Center, Technology Research Laboratory, Shimadzu Corporation, Kyoto 604‑8511, Japan., Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305‑8575, Japan.